Stuhlmann and Falck(83) (1857) were the first to make a study of the toxicity of caffein on animals of different species. The administration of 0.5 gram of caffein subcutaneously or per rectum in rabbits induced tremors, tonic and clonic convulsions, paralysis, and increased frequency of respiration at first followed by violent dyspnoea. On autopsy he noticed congestion of the organs and in two of the three rabbits experimented upon punctiform hemorrhages of the brain with congestion of the meninges were found. In the other rabbit anemia of the brain was observed. Experiments on cats were carried out by subcutaneous, intravenous, and rectal injections. The symptoms observed after the administration of 0.5 to 0.7 gram of caffein were the same as in rabbits except that the cats developed diarrhea when caffein was given and no anatomic lesions were found on autopsy. The effect of caffein on dogs indicated that in subjects of medium weight a dose of 0.5 gram given by mouth might produce restlessness and increased frequency of respiration, while the injection of the same amount intravenously into such animals may cause death. Large, full-grown dogs, however, survived an intravenous injection of 2 grams of caffein, showing symptoms of incoordination, salivation, and frequent defecation. These investigators also made observations on caffein, using pigeons and other birds; 0.5 to 0.1 gram introduced into the stomach caused vomiting, diarrhea, tonic, but more frequently clonic, convulsions, incoordination, tremors, paresis, and paralysis. In a few, but not in all of the birds, there was at first increased frequency of respiration followed by dyspnoea and circulatory disturbances. These amounts of caffein proved fatal in all of the experiments on birds. Inflammation of the intestinal mucosa and congestion of the meninges were the only changes found on autopsy. Stuhlmann and Falck also studied the effects of caffein on fishes and toads. Mitscherlich(60) (1858) fed 0.4 gram of caffein with bread to a rabbit and noticed lowered temperature, fatigue, convulsions, first increased then decreased frequency of respiration, and on autopsy congestion of all the viscera. He also reported observations on two frogs, one of which was given one-sixteenth of a grain of caffein in a pill with bread. It was administered to the other frog in aqueous solution, but the mode of administration was not published. The symptoms observed were in the main the same as in rabbits. In pigeons 0.125 gram introduced into the stomach caused severe vomiting, muscular incoordination, tonic rigidity of the limbs, and retraction of the head. Respiration was increased in frequency. Death followed within 3 hours and 15 minutes.